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prevalence of AD
approx 6M
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is early or late onset of AD more common
late, often sporadic 70%, >65
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onset of familial AD
rare (<5%), onset < 40
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3 susceptibility genes for AD
- amyoid presursor protein APP
- presenilin I & II
- Apo E4
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5 morphological atrophy's of AD
- diffuse cortical atrophy
- increase ventricular volume
- atrophy of gyri
- enlargement of sulci
- hippocampal atrophy
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3 imaging techniques for AD & explain
FDG - reveals metabolic deficits by assessing glucose utilisation rate
Pittsburgh Compound B - radiotracer for imaging amyloid paques by positron emission tomography
In Vivo human imaging - imaging for amyloid deposits by positron emission tomography (PET)
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cognitive changes in AD
gradual decline in memory, cognition and function
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a complication from AD
weight loss - may be due to infection, wandering, problems eating
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7 cognitive and functional declines in AD
- decrease new memory acquisition
- aphasia - decrease language
- apraxia - decrease performing sequential motor tasks
- anosognosia - pt unaware of his/her own difficulties
- navigational difficulties
- sleep difficulties
- shuffling gait in some pts, but w/o the tremor of PD
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five stages of AD
- MCI
- early
- middle
- late
- end-stage
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give the order of top 3 impairments from AD
- memory
- language
- visuospatial
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3 factors of MCI in AD
- syndromic designation
- categorizes pts with cognitive complaints, but insufficient to warrant a syndromic diagnosis of dementia
- 10% to 15% chance/yr of AD
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3 main histopathology of AD
- amyloid plaques
- neurofibrillary tangles
- Abeta42 amyloid in arterial walls of cerebral blood vessels
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what are neurofibrillary tangles of AD
highly phosphorylated tau protein
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3 characteristics of amyloid plaques
- senile plaques with Abeta amyloid
- smaller soluble oligomers are receiving more attention as the possible more toxic moiety
- oligomers accumulate to form plaques
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In AD which 2 neurotransmitters do you have a progressive loss of
- cholinergic neurons
- principal cortical neurons
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in AD what enzyme and receptor do you have progressive loss of
- acetylcholinesterase
- nicotinic acetylcholine receptors
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what are the 2 molecular changes in plaques in AD
- amyloid precursor protein
- presenilin I & II
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what toxin results from cleaving beta-secretase
Abeta 42
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give the steps of APP cleavage
- alpha or beta secretase cleavage
- beta secretase cleavage by gamma-secretase to Abeta 42(toxic) or A beta 40 (nontoxic)
- alpha secretase cleaved by gamma secretase to P3 (nontoxic)
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6 treatable causes of dementia to rule out
- brain tumors
- thyroid disease
- vitamin deficiencies
- drug & Rx toxicities
- chronic infection
- severe depression (pseudodementia)
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